The disease course of Castleman disease patients with fatal outcomes in the <scp>ACCELERATE</scp> registry

Fajgenbaum, David C; Pierson, Sheila K; Kanhai, Karan; Bagg, Adam; Alapat, Daisy; Lim, Megan S.; Lechowicz, Mary Jo; Srkalović, Gordan; Uldrick, Thomas S.; Rhee, Frits van

doi:10.1111/bjh.18214

Cited by 3 publications

(1 citation statement)

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“…Analysis of the patients with thrombocytopenia was not performed because of the very low sample size; however, there is evidence that patients with iMCD with low platelet levels are at increased risk of fatal outcomes. 5,14 Similarly, we observed that iMCD-related symptoms abated relatively quickly in a large portion of patients. This is consistent with a realworld Polish study involving 11 patients treated with siltuximab, in which best symptomatic response was observed in most cases after the fourth treatment cycle (range, 3-9 cycles).…”

Section: Discussionsupporting

confidence: 65%

Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease

Rhee

Rosenthal²,

Kanhai

et al. 2022

Blood Advances

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Idiopathic multicentric Castleman disease (iMCD) is a rare, heterogeneous disorder involving multicentric lymphadenopathy, systemic inflammation, and cytokine-driven organ dysfunction. Despite the approval of siltuximab-a monoclonal antibody against interleukin-6-for the treatment of iMCD, it is not known how long patients should receive siltuximab before determining whether the treatment is beneficial and should be continued. We performed post hoc analyses of the phase 2 randomized, double-blind, placebo-controlled trial of siltuximab for the treatment of patients with iMCD (NCT01024036) to determine the sequence of normalization of laboratory, clinical, and lymph node responses in patients who responded to siltuximab. Seventy-nine patients were enrolled in the trial (n=53 siltuximab; n=26 placebo plus best supportive care). Progression-free survival (PFS) was significantly improved in siltuximab-treated patients compared with placebo (P=0.0001). The median PFS was 14.5 months (95% CI, 13.6-upper bound not reached) for patients on placebo, but not reached for patients on siltuximab. In siltuximab-treated patients who achieved a durable tumor (radiologic) and symptomatic response (18/53 [34%]), the median time to normalization of abnormal laboratory tests and clinical endpoints occurred in the following sequence: thrombocytosis, symptomatic response, elevated C-reactive protein, hypoalbuminemia, anemia, lymph node response, hyperfibrinogenemia, and elevated immunoglobulin G. Siltuximab treatment prolongs PFS, rapidly improves symptomatology, and provides meaningful clinical benefit despite some laboratory tests and enlarged lymph nodes taking months to normalize in treatment responders. These data support the continued front-line use of siltuximab for iMCD, as recommended by international guidelines.

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Section: Discussionsupporting

confidence: 65%